Epidural administration of morphine is a common clinical practice to provide satisfactory analgesia for acute postoperative pain. Scientific evidence results from numerous studies conducted in a clinical pain setting. However, these conditions do not allow investigators to address many questions concerning the pharmacodynamics of epidural morphine. The goal for the current study is to employ a recently developed experimental pain model to study the spread and the time course of analgesia mediated by epidural morphine. To our knowledge this is the first randomized, placebo controlled, double-blind, cross-over study investigating the pharmacodynamics of epidural morphine for a 24 hour period post injection. Analysis of the available data suggests that the onset of analgesia after epidural morphine is very slow, peak effect occurs not before five hours and the drug acts for at least 24 hours. Additionally there is reasonable evidence to suggest that epidural morphine acts mainly by diffusion to the spinal cord as opposed to a systemic re-uptake. Suggested experimental pain model is a suitable pharmacodynamic tool to depict analgesia mediated by epidural morphine.